{"title":"BBOX1-IP3R3相互作用的计算感知揭示了三阴性乳腺癌中钙信号失调的抑制剂。","authors":"P Sangavi, G R Shri, S K Singh, K Langeswaran","doi":"10.1080/1062936X.2025.2497380","DOIUrl":null,"url":null,"abstract":"<p><p>Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer unveiling negative expression on oestrogen receptors, progesterone receptors, and HER2. The anomalous activation of signalling pathways and specific types of mutations characterize the progression of TNBC. Protein-protein interaction in the tumour microenvironment plays a crucial role in tumour aggressiveness. Disrupting the signalling pathways that promote cell progression, migration, and survival opens up a promising avenue for targeting the aggressive form of TNBC. The present study emphasizes the molecular interaction mechanism driving the aggressive and recalcitrant TNBC between BBOX1-IP3R3. The BBOX1-IP3R3 complex destabilization was accomplished using compounds obtained from various databases through virtual screening, molecular, and essential dynamics. The interaction study revealed that the four hits bound at the interface and facilitated better binding affinity with the highest docking score and optimal binding free energy. In addition, the molecular dynamics simulation, PCA/FEL, and MM/PBSA analysis conclusively evaluate the binding potential of the compounds and unequivocally stabilize specific conformations or deception of the complexes in high-energy states. Thus, the identified compounds lead to the disruption of BBOX1-IP3R3 interaction, which aids in the therapeutic option of TNBC.</p>","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"305-332"},"PeriodicalIF":2.3000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A computational perception of BBOX1-IP3R3 interaction uncovers inhibitors for dysregulated calcium signalling in triple negative breast cancer.\",\"authors\":\"P Sangavi, G R Shri, S K Singh, K Langeswaran\",\"doi\":\"10.1080/1062936X.2025.2497380\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer unveiling negative expression on oestrogen receptors, progesterone receptors, and HER2. The anomalous activation of signalling pathways and specific types of mutations characterize the progression of TNBC. Protein-protein interaction in the tumour microenvironment plays a crucial role in tumour aggressiveness. Disrupting the signalling pathways that promote cell progression, migration, and survival opens up a promising avenue for targeting the aggressive form of TNBC. The present study emphasizes the molecular interaction mechanism driving the aggressive and recalcitrant TNBC between BBOX1-IP3R3. The BBOX1-IP3R3 complex destabilization was accomplished using compounds obtained from various databases through virtual screening, molecular, and essential dynamics. The interaction study revealed that the four hits bound at the interface and facilitated better binding affinity with the highest docking score and optimal binding free energy. In addition, the molecular dynamics simulation, PCA/FEL, and MM/PBSA analysis conclusively evaluate the binding potential of the compounds and unequivocally stabilize specific conformations or deception of the complexes in high-energy states. Thus, the identified compounds lead to the disruption of BBOX1-IP3R3 interaction, which aids in the therapeutic option of TNBC.</p>\",\"PeriodicalId\":21446,\"journal\":{\"name\":\"SAR and QSAR in Environmental Research\",\"volume\":\" \",\"pages\":\"305-332\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"SAR and QSAR in Environmental Research\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://doi.org/10.1080/1062936X.2025.2497380\",\"RegionNum\":3,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"SAR and QSAR in Environmental Research","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1080/1062936X.2025.2497380","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
A computational perception of BBOX1-IP3R3 interaction uncovers inhibitors for dysregulated calcium signalling in triple negative breast cancer.
Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer unveiling negative expression on oestrogen receptors, progesterone receptors, and HER2. The anomalous activation of signalling pathways and specific types of mutations characterize the progression of TNBC. Protein-protein interaction in the tumour microenvironment plays a crucial role in tumour aggressiveness. Disrupting the signalling pathways that promote cell progression, migration, and survival opens up a promising avenue for targeting the aggressive form of TNBC. The present study emphasizes the molecular interaction mechanism driving the aggressive and recalcitrant TNBC between BBOX1-IP3R3. The BBOX1-IP3R3 complex destabilization was accomplished using compounds obtained from various databases through virtual screening, molecular, and essential dynamics. The interaction study revealed that the four hits bound at the interface and facilitated better binding affinity with the highest docking score and optimal binding free energy. In addition, the molecular dynamics simulation, PCA/FEL, and MM/PBSA analysis conclusively evaluate the binding potential of the compounds and unequivocally stabilize specific conformations or deception of the complexes in high-energy states. Thus, the identified compounds lead to the disruption of BBOX1-IP3R3 interaction, which aids in the therapeutic option of TNBC.
期刊介绍:
SAR and QSAR in Environmental Research is an international journal welcoming papers on the fundamental and practical aspects of the structure-activity and structure-property relationships in the fields of environmental science, agrochemistry, toxicology, pharmacology and applied chemistry. A unique aspect of the journal is the focus on emerging techniques for the building of SAR and QSAR models in these widely varying fields. The scope of the journal includes, but is not limited to, the topics of topological and physicochemical descriptors, mathematical, statistical and graphical methods for data analysis, computer methods and programs, original applications and comparative studies. In addition to primary scientific papers, the journal contains reviews of books and software and news of conferences. Special issues on topics of current and widespread interest to the SAR and QSAR community will be published from time to time.